The present invention relates to a method of treating viral infection wherein the transcription or translation of viral genes or the replication of the virus is inhibited by administering an N-acylcysteine to restore thiol balance.
It is known that HIV-infected individuals have low levels of serum acid-soluble thiols and low levels of intracellular glutathione (GSH) in peripheral blood mononuclear cells (PBMC) [Eck et al., Biol. Chem. Hoppe-Seyler, 370:101-108, 1989]. Asymptomatic HIV-seropositive patients have dramatically reduced GSH levels in lung epithelial lining fluid and in blood plasma [Buhl et al., Lancet, ii:1294-1298, 1989]. Tumor necrosis factor (TNF-.alpha.) stimulates HIV transcription and viral protein production in vitro by activating the DNA binding protein NF.gamma.B which in turn increases the promoter activity of the HIV long terminal repeat and thereby increases HIV mRNA and protein levels.
TNF-.alpha. levels are abnormally high in serum samples from AIDS patients and rise as opportunistic infections become more frequent in patients with ARC and AIDS. Some of the toxic effects of TNF-.alpha. are exerted by stimulation of an intracellular oxidative (respiratory) burst which generates reactive oxidative intermediates (ROI's). Phorbol 12-myristate 13-acetate (PMA) mimics the oxidant stimulating action of TNF-.alpha.. Intracellular oxidants/ROI's are scavenged by intracellular GSH, but high levels of oxidants or depressed levels of GSH result in vulnerability to cytotoxic effects.
In a related, copending application, U.S. Ser. No. 07/459,997 (pending), filed Jan. 5, 1990, and its predecessor applications, the therapeutic effect of N-acylcysteines for HIV-infected patients is disclosed, including its antiviral effects. A need continues to exist for a general method for antiviral therapy and inhibition of expression of viral genetic material.